Axillary sentinel node biopsy after neoadjuvant chemotherapy

Introduction

The role of sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC) with potentially sterilized axillary lymph nodes after neoadjuvant chemotherapy (NAC) remains unclear.

Patients and methods

Between 2002 and 2008, SLNB with both blue-dye and radioisotope injection was performed in 77 patients with LABC whose cytopathologically confirmed positive axillary node(s) became clinically negative after NAC. Factors associated with SLN identification and false-negative rates, presence of non-sentinel lymph node (non-SLN) metastasis were analyzed retrospectively.

Results

SLNB was successful in 92% of the patients. Axillary status was predicted with 90% accuracy and a false-negative rate of 13.7%. Patients with residual tumor size >2 cm had a decreased SLN identification rate (p = 0.002). Axillary nodal status before NAC (N2 versus N1) was associated with higher false-negative rates (p = 0.04). Positive non-SLN(s) were more frequent in patients with multifocal/multicentric tumors (versus unifocal; p = 0.003) and positive lymphovascular invasion (versus negative; p = 0.0001). SLN(s) positive patients with pathologic tumor size >2 cm (versus ≤2 cm; p = 0.004), positive extra-sentinel lymph node extension (versus negative; p = 0.002) were more likely to have metastatic non-SLN(s).

Conclusions

SLNB has a high identification rate and modest false-negative rate in LABC patients who became clinically axillary node negative after NAC. Residual tumor size and nodal status before NAC affect SLNB accuracy. Additional involvement of non-SLN(s) increases with the presence of multifocal/multicentric tumors, lymphovascular invasion, residual tumor size >2 cm, and extra-sentinel node extension.     

Prognostic influence of immunohistochemically detected lymph node micrometastasis and histological subtype in pN0 oesophageal cancer

Introduction

Differences in frequency and clinical impact of lymph node micrometastasis between histological subtypes of oesophageal cancer have not been determined.

Methods

1204 lymph nodes from 32 squamous cell carcinomas and 54 adenocarcinomas with complete resection and pN0 status were re-evaluated using a serial sectioning protocol including immunohistochemistry. Intra-nodal tumour cells were classified as micrometastases (0.2–2 mm) or isolated tumour cells (<0.2 mm).

Results

There was no significant difference in the frequency of micrometastases between adenocarcinoma and squamous cell carcinoma (11.3% vs. 3.1%, p = n.s.). In the squamous cell carcinoma group, Kaplan–Meier curves showed a significantly prolonged 5-year survival (p = 0.02) and disease free interval (p < 0.01) for immunohistochemically node negative versus node positive patients. In patients with adenocarcinoma, no such difference (p = n.s. and p = n.s., respectively) was seen. In patients who did not undergo pre-treatment, those with adenocarcinoma had a significant 5-year survival (65% vs. 53%; p = 0.03) and disease free interval (83% vs. 58%; p < 0.05) advantage over those with squamous cell carcinoma. After pre-treatment, no difference between the histological subtypes was detected.Regression analysis did not reveal any factors that significantly affected overall survival in node negative patients. However, four factors did significantly influence disease free interval: pre-treatment (HR 3.3 [95% CI 1.2–9.1], p = 0.02); micrometastasis (HR 5.3 [95% CI 1.4–19.7], p = 0.01); UICC stage II vs. 0/I (HR 2.2 [95% CI 1.1–4.4], p = 0.03); and adenocarcinoma (HR 0.3 [95% CI 0.1–0.9], p = 0.03).

Conclusion

The difference in frequency and clinical impact of immunohistochemically detected micrometastasis may indicate that adenocarcinoma and squamous cell carcinoma should not be treated as one entity.     

Lymphatic mapping in patients with primary or recurrent breast cancer following previous axillary surgery

Aims

To evaluate the feasibility of lymphatic mapping in breast cancer patients after previous axillary surgery and to identify parameters associated with mapping failure.

Methods

Lymphatic mapping using peritumoural injection of blue dye and a radiocolloid was attempted in 30 patients with primary (n = 7) or recurrent (n = 23) breast cancer and a history of previous axillary lymph node dissection or sentinel node biopsy.

Results

Lymphatic mapping identified a mean number of 1.6 (range 1–3) lymph nodes in 19 of 30 patients (identification rate 63%). The lymph nodes were removed from the ipsilateral axilla (n = 13), the internal mammary chain (n = 2), both the internal mammary nodes and the axilla (n = 2), the interpectoral space (n = 1) and the contralateral axilla (n = 1). Four of 19 patients revealed a positive lymph node. Fifteen of 19 patients had a negative lymph node. Axillary lymph node dissection was done in 13 of 15 patients but found no positive nodes (false negative rate = 0). A negative lymphoscintigram (p < 0.001) and a number of more than 10 lymph nodes removed at the time of initial surgery (p = 0.02) were significantly associated with a mapping failure.

Conclusion

Lymphatic mapping following prior axillary surgery was accurate but associated with a low identification rate. The lymphatic drainage pattern was unpredictable and the use of a radionuclide was necessary for a successful mapping procedure.     

Outcomes for a large series of radical cystectomies for bladder cancer

Aims

We present the characteristics and outcomes of a large Chinese series of patients treated with radical cystectomy and pelvic lymphadenectomy for invasive cancer of the bladder. Our aim is to determine the significant independent prognostic factors that determine this outcome.

Methods

The records of 356 patients with invasive bladder cancer, operated at three Chinese medical institutes between 1995 and 2004, were reviewed. Of the 356 patients, 324 (91.0%) were TCC, 24 (6.7%) were adenocarcinoma, eight (2.3%) were squamous carcinoma. The incidence of pelvic lymph node involvement was 22.8%. The mean (SD, range) follow-up of the 356 patients was 54.89 (31.66, 3–137) months. Multivariate analysis was used to assess the clinical and pathological variables affecting disease-free survival (DFS).

Results

The 1-, 2- and 5-year DFS rates were 87%, 75% and 48%, respectively. In multivariate analysis, tumor configuration (RR = 1.62, p = 0.012), multiplicity (RR = 1.41, p = 0.036), histological subtype (RR = 2.17, p < 0.001), tumor stage (RR = 2.50, p < 0.001), tumor grade (RR = 2.40, p < 0.001), node status (RR = 2.51, p < 0.001), neoadjuvant chemotherapy (RR = 0.46, p = 0.016) had independent significance for survival on multivariate analysis.

Conclusions

The results of this series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and DFS in patients with invasive bladder cancer. Multivariates affect the prognosis after radical cystectomy for invasive bladder cancer. The treatment of invasive bladder cancer in China is still in need of improvement and normalization.     

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients

Objective

The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96–98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND).

Methods

Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, pN0/pN_SN0) were assessed from our prospective database. Patients underwent either ALND (n = 178) in 1990–1997 or SLN biopsy (n = 177) in 1998–2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen.

Results

The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p = 0.008) and overall survival (p = 0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10–0.73, p = 0.009) and overall survival (HR: 0.34, 95% CI: 0.14–0.84, p = 0.019).

Conclusions

This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.     

Patterns of lymph node spread and its influence on outcome in resectable parotid cancer

Aim

To assess the metastatic topography of intraparotideal and neck lymph nodes in parotid cancer and its influence on tumour recurrence and survival.

Methods

The lymph node spread of 142 patients with primary parotid carcinoma treated from 1986 to 2006 was analysed. Disease-free survival (DFS) and overall survival (OS) were calculated. The role of the metastatic pattern as prognostic factors were univariately and multivariately analysed.

Results

A lateral, total or radical parotidectomy was performed in 19, 80 and 43 patients, respectively. A radical/radical-modified or selective neck dissection was performed in 68 and 74 patients, respectively. Eighty-seven neck dissection specimens were negative (pN0). Twelve patients had intraparotideal and cervical lymph node involvement (pPar+/pN+). In 24 patients only intraparotideal metastases were detected (pPar+/pN0). 19 patients only had cervical nodal involvement (pPar−/pN+). Twenty-five patients had occult locoregional lymph metastases (cN0/pN+). The median follow-up was 24.4 months. The disease-free survival rate was 81% at 5 years, and 62% at 10 years. By univariate analysis, R+ (p = 0.001), pT (p = 0.019), lymphangiosis carcinomatosa (p = 0.019), pN+ (p = 0.042), and extracapsular spread (p = 0.046) were prognostic for disease-free survival. Multivariate analysis revealed R+ as independent risk factor (p = 0.046). In pN+ patients, involvement of parotid lymph nodes (p = 0.013), nodes in neck level I (p < 0.0001) and IV (p = 0.005) were univariate risk factors. Multivariate analysis showed lymph node metastases in level I as independent risk factor (p = 0.022).

Conclusion

Total parotidectomy and radical-modified neck dissection is recommended as surgical treatment of parotid cancer and should be analysed in a prospective trial.     

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

Aim

To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS).

Materials and methods

Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan–Meier were performed.

Results

Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p < 0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR = 5.6, p < 0.001), positive SN (RR = 5.0, p < 0.001) and male sex (RR = 2.9, p = 0.001). The presence of a metastatic SN (RR = 8.4, p < 0.001), male sex (RR = 6.1, p < 0.001), Breslow thickness (RR = 3.2, p = 0.013) and ulceration (RR = 2.6, p = 0.015) were significantly associated with a poorer DSS.

Conclusion

SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure.     

The prognostic significance of extracapsular lymph node involvement in node positive patients with colonic cancer

Aims

In colonic cancer the prognostic significance of extracapsular lymph node involvement (LNI) is not established and is therefore the objective of this study.

Methods

Between January 1994 and May 2005, all patients who underwent resection for primary colonic cancer with lymph node metastasis were reviewed. All resected lymph nodes were re-examined to assess extracapsular LNI. In uni- and multivariate analysis disease-free survival (DFS) was correlated with various clinicopathologic factors.

Results

One hundred and eleven patients were included. In 58 patients extracapsular LNI was identified. Univariate analysis revealed that pN-stage (5-year DFS pN1 vs. pN2: 65% vs. 14%, p < 0.001), extracapsular LNI (5-year DFS intracapsular LNI vs. extracapsular LNI: 69% vs. 41%, p = 0.003), and lymph node ratio (5-year DFS <0.176 vs. ≥0.176: 67% vs. 42%, p = 0.023) were significant prognostic indicators. Among these variables pN-stage (hazard ratio 3.5, 95% confidence interval [CI]: 1.72–7.42) and extracapsular LNI (hazard ratio 1.98, 95% CI: 1.00–3.91) were independent prognostic factors. Among patients without extracapsular LNI, those receiving adjuvant chemotherapy had a significantly better survival (p = 0.010). In contrast, chemotherapy did not improve DFS in patients with extracapsular LNI.

Conclusion

Together with pN2 stage, extracapsular LNI reflects a particularly aggressive behaviour and has significant prognostic potential.     

The clinical outcome and prognostic factors after multi-visceral resection for advanced colon cancer

Aim

The value of multi-visceral resection (MVR) for treating primary advanced colon cancer infiltrating into the neighboring organs had been debated because of the high mortality.

Methods

We reviewed 1288 patients who underwent curative resection for pT3–4 colon cancer without distant metastasis from 1994 to 2004.

Results

Eighty four patients (6.5%) with colon cancer infiltrating into the neighboring organs (cT4) underwent MVR. The accuracy of the intra-operative decision for true invasion (pT4) was 35.7%. Major surgical morbidity occurred in 11 patients of the standard resection group (0.9%) and in 2 patients of the MVR group (2.3%) (p = 0.206). Most of the recurrence was distant metastasis (20 patients, 23.8%). Local recurrence was occurred in five patients (6.0%). The prognostic factors for recurrence and survival were pathologic tumor invasion (p = 0.033 and p = 0.016, respectively) and lymph node metastasis (p = 0.010 and p < 0.001, respectively).

Conclusion

Multi-visceral resection was a safe and curative procedure as compared with standard resection for patients with advanced colon cancer. The cause of a poor prognosis in MVR was not local recurrence but distant metastasis. Pathologic tumor invasion and lymph node metastasis were the potential prognostic factors.     

Improving staging accuracy in colon and rectal cancer by sentinel lymph node mapping: A comparative study

Aim

To compare the predictive value of sentinel lymph node (SN) mapping between patients with colon and rectal cancer.

Patients and methods

An ex vivo SN procedure was performed in 100 patients with colon and 32 patients with rectal cancer. If the sentinel node was negative, immunohistochemical analyses using two different antibodies against cytokeratins (Cam5.2 and CK 20) and one antibody against BerEp-4 were performed to detect occult tumour cells. Isolated tumour cells (<0.2 mm) were discriminated from micrometastases (0.2–2 mm).

Results

An SN was identified in 117 patients (89%), and accurately predicted nodal status in 106 patients (accuracy 91%). Both sensitivity and negative predictive value were higher in colon carcinomas than in rectal carcinomas (83% versus 57%, p = 0.06 and 93% versus 65%, p = 0.002 respectively). In patients with extensive lymph node metastases the SN procedures were less successful. Eleven of the 13 unsuccessful SN procedures were performed in patients with rectal cancer who had pre-operative radiotherapy. After immunohistochemical analysis 21 of the 73 N0 patients had occult tumour cells in their SN; eight patients had micrometastases and 13 patients had isolated tumour cells.

Conclusion

SN mapping accurately predicts nodal status in patients with colonic cancer. Immunohistochemical analysis demonstrates micrometastatic disease in eight out of 73 N0 patients, with a true upstaging rate of 11%. SN mapping is less reliable in patients with rectal cancer after pre-operative radiotherapy.     

Improvements in breast cancer survival over time,related to adjuvant treatment and node status

Background

There has been an increase in the use and effectiveness of adjuvant treatment for operable breast cancer and the aim of this study was to examine whether this has resulted in improved survival for all prognostic groups.

Methods

A retrospective study of 1517 patients with invasive breast cancer treated between 1980 and 2002 was carried out. The use of adjuvant treatment was compared between two time periods in patients based on nodal status, and survival was calculated by Kaplan–Meier life table analysis. Independent predictors for recurrence-free survival (RFS) were determined by Cox regression analysis.

Results

The use of adjuvant therapy increased for all prognostic groups. On multivariate analysis the use of radiotherapy and endocrine therapy was positively associated with RFS which was significant in the second time period. Outcome in node positive patients improved: five-year RFS from 59% to 76%, p < 0.01 and breast cancer specific survival (BCSS) from 70% to 83%, p < 0.01. However, there was no survival improvement in the larger group of node negative patients; BCSS 93% versus 95%, p = 0.99. Within the node negative group, patients with tumours ≥ 2 cm had an improved RFS from 80% to 88%, p = 0.02.

Conclusion

The increased use of adjuvant therapy was associated with an improved outcome in node positive patients. For node negative patients with good prognostic features the evidence of benefit was marginal.     

Outcome of distal gastric cancer with pyloric stenosis after curative resection

Aims

Pyloric stenosis usually presents with symptoms, and this may lead patients to consult their physician. We evaluate whether distal gastric cancer patients with pyloric stenosis had a better outcome than those without.

Methods

A total of 551 distal gastric cancer patients who received curative subtotal gastrectomy between January 1988 and December 2003 at Taipei Veterans General Hospital were analyzed. Among them, 174 patients were sorted into the pyloric stenosis group according to obstructive symptoms. Their clinicopathological features, survival and prognostic factors were evaluated.

Results

The 5-year overall and disease-free survival rate of distal third gastric adenocarcinoma for the pyloric stenosis group was significantly lower than those without pyloric stenosis. Multivariate analysis revealed the pyloric stenosis group had deeper cancer invasion (relative to pT₁, RR of pT₂ 3.1, p = 0.009; pT₃ 6.1, p < 0.001; pT₄ 16.5, p < 0.001), and more lymph node metastasis (RR 3.6; p = 0.001). The pyloric stenosis group had a tendency to lymph node metastasis toward the hepatoduodenal ligament, but this did not reach statistical difference. However, the pyloric stenosis group had significantly higher lymph node metastasis in the retropancreatic region (5.17% vs. 0.53%; p = 0.001).

Conclusions

Distal gastric cancers with pyloric stenosis have worse biological behavior than those without, and consequently have a poor outcome.     

Prediction of rectal lymph node metastasis by pelvic computed tomography measurement

Aim

Rectal cancer staging represents a crucial step to select the best treatment for this tumour. Particularly after neo-adjuvant chemoradiotherapy (CRT), it may influence the surgical procedure (e.g. radical resection vs. local excision). The aim of this study was to determine the best lymph node size cut-off at computed tomography (CT) to predict nodal metastasis in rectal cancer patients with and without preoperative CRT.

Methods

A consecutive series of patients operated on for primary mid–low rectal adenocarcinoma, all staged with pelvic CT scan, were subdivided as follows: those who underwent surgery alone treatment without CRT (Group A) and those who underwent preoperative CRT (Group B). All CT scans were re-viewed by a single radiologist and, based on the lymph node size, findings were compared with pathologic lymph node status (pN). At each lymph node size cut-off value, the following were calculated: accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The best cut-off value was defined as having an accuracy ≥70% with the highest NPV.

Results

The study population consisted of 162 patients: Group A (n = 52) and Group B (n = 110). Patients classified as pN-positive (n = 45) had a higher number of and larger sized lymph nodes by CT scan than patients classified as pN-negative (n = 117). The cut-off values with an accuracy ≥70% ranged between 7 and 11 mm in Group A and between 9 and 14 mm in Group B. The cut-off with the best NPV was 7 mm for Group A and 10 mm for Group B.

Conclusions

Acknowledging the limitations of the dimensional criterion, lymph node size cut-off values found in our study may be useful for planning rectal cancer treatment using CT scan.     

Factors predicting the sentinel node metastases in T1 breast cancer tumor:An analysis of 1416 cases

Aim

To determine the factors associated with the metastatic involvement of sentinel lymph node (SLN) biopsy in patients with early breast cancer.

Study design

This was a retrospective study of patients with T1 invasive breast cancer who underwent SLN biopsy at Claudius Regaud Institute between January 2001 and September 2008.

Results

1416 patients were recruited into this study. SLN metastases were detected in 368 patients (26%). Younger age, tumor size and location, histological type, nuclear grade, and lymphovascular invasion appear to be significant risk factors of SNL involvement. In multivariate analysis, tumor size, tumor location, histological type and lymphovascular invasion are significant factors. When the tumor size is >20 mm, the OR is 6.6 compared to a T1a tumor (3.145–14.175, p < 0.001, confidence interval 95%). When the tumor is found in the inner quadrant, the risk of SLN involvement is reduced compared to external locations with an OR of 0.53 (0.409–0.709, p < 0.001, confidence interval 95%). Non-ductal/lobular compared to infiltrative ductal cancer have a lower risk of SLN involvement with an OR of 0.423 (0.193–0.927, p < 0.03, confidence interval 95%). Lymphovascular invasion increase the risk of positive SLN with an OR of 2.8 (1.9–4.1, p < 0.001, confidence interval 95%).

Conclusion

It appears reasonable to avoid axillary lymph node dissection in older patients with T1a tumors of good histopathological type and in the absence of lymphovascular invasion.     

Validation over time of a nomogram including HER2 status to predict the sentinel node positivity in early breast carcinoma

Background

The molecular subtypes of breast cancer have different axillary status. A nomogram including the interaction covariate between estrogen receptor (ER) and HER2 has been recently published (Reyal et al. PLOS One, May 2011) and allows to identify the patients with a high risk of positive sentinel lymph node (SLN). The purpose of our study was to validate this model on an independent population.

Methods

We studied 755 consecutive patients treated at Institut Curie for operable breast cancer with sentinel node biopsies in 2009. The multivariate model, including age, tumor size, lymphovascular invasion and interaction covariate between ER and HER2 status, was used to calculate the theoretical risk of positive sentinel lymph node (SLN) for all patients. The performance of the model on our population was then evaluated in terms of discrimination (area under the curve AUC) and of calibration (Hosmer–Lemeshow HL test).

Results

our population was significantly different from the training population for the following variables: median tumor size in mm, lymphovascular invasion, positive ER and age. The nomogram showed similar results in our population than in the training population in terms of discrimination (AUC = 0.72 [0.68–0.76] versus 0.73 [0.7–0.75] and calibration (HL p = 0.4 versus p = 0.35).

Conclusions

Despite significant differences between the two populations concerning variables which are part of the nomogram, the model was validated in our population. This nomogram is robust over time to predict the likelihood of positive SLN according to molecular subtypes defined by surrogate markers ER and HER2 determined by immunohistochemistry in clinical practice.     

Sentinel node biopsy in breast cancer has a greater node positivity rate than axillary node sample: Results from a retrospective analysis

Background

Sentinel node biopsy as a surgical method of axillary staging for early breast cancer has been widely accepted as an alternative to traditional four-node axillary node sampling, and is the recommended technique by the Association of Breast Surgery in the United Kingdom. In selected units axillary sampling has been compared with either radioisotope sentinel node or blue dye only techniques with comparable node positivity rates. There are no studies directly comparing combined method sentinel node biopsy (SNB) with conventional axillary (four) node sampling (ANS).

Methods

Data for all patients undergoing axillary staging by axillary node sample or sentinel node biopsy were collected, including those proceeding to axillary clearance as a second procedure, but excluding those undergoing axillary clearance as a first procedure.

Results

From January 2005 to January 2011, 641 axillary staging procedures were performed (SNB n = 231 (36.0%), ANS n = 410 (64.0%)). Baseline tumour characteristics were similar for the two groups except for a higher frequency of breast conservation in the SNB group (95.6 vs. 75.6%; p < 0.0001). The proportion of cases with positive nodes was higher in the SNB group (20.8 vs. 14.4%; p = 0.042). In patients who had presented with symptomatic disease, there was a significantly higher node positivity rate with SNB (30.9%) than with ANS (15.5%; p = 0.002), despite similar baseline characteristics in both groups.

Conclusion

Combined method sentinel node biopsy is more sensitive at detecting low volume axillary disease than traditional four-node sample.     

A prospective randomized trial: The influence of intraoperative application of fibrin glue after radical inguinal/iliacal lymph node dissection on postoperative morbidity

Background

Effects of intraoperative application of fibrin glue following combined radical inguinal and iliacal lymph node dissection (RILND) on the amount of postoperative lymphatic secretion are discussed controversially. To detect whether fibrin glue application results in a decreased lymphatic secretion following RILND a randomized patient blinded clinical trial was conducted.

Method

Between September 2003 and September 2006 58 patients with stage IV melanoma underwent therapeutic RILND and were randomized into two groups. 29 Patients received 4 cc fibrin glue after RILND whereas 29 patients were only irrigated with saline 0.9 percent. Postoperatively all patients received two inguinal and one iliacal closed suction drain. The main outcome criteria were the duration of drain placement in the wound. Minor criteria were the total amount of secretion and the length of hospital stay.

Results

There was no difference between the treatment and the control group in the duration of drain placement (fibrin group: 4 days (1–27); control group 5 days (1–26); p = 0.64). The total amount of fluid was 310 cc (30–6005) in the fibrin group vs. 365 cc (30–3945 cc) in the control group (p = 0.9) and the length of hospital stay 10 days (3–41) (group 1) compared to 11 days (3–41) (p = 0.99) were not different between both groups either.

Conclusion

Intraoperative application of 4 cc fibrin glue does not reduce the length of drain placement, drain output or hospitalisation of patients undergoing RILND with melanoma metastasis to the lymph node basin.     

Markers of tumour angiogenesis and tumour cells in bone marrow in gastric cancer patients

Aims

Vascular endothelial growth factors VEGF-A, VEGF-C and VEGF-D are considered to be potentially angiogenetic and lymphangiogenetic. “Minimal residual disease” is responsible for cancer progression and recurrence. In this study, we investigated the relation between expressions of VEGF-A, VEGF-C and VEGF-D in gastric cancer tissue and the presence of tumour cells in bone marrow.

Methods

A total of 50 resected primary gastric adenocarcinomas, 44 non-cancerous gastric mucosa and 36 lymph node metastases were analyzed by immunohistochemistry for VEGF-A, VEGF-C and VEGF-D. The specimens used were drawn from a previous study cohort, where the presence of ITC in bone marrow was confirmed with immunohistochemical assay with cytokeratin (CK)-18.

Results

The levels of expression of VEGF-A, VEGF-C and VEGF-D were highest in tumour (p < 0.001), and the level in lymph node metastases was significantly higher (p < 0.01) than in mucosa. The expression of VEGF-A was correlated significantly with venous tumour invasion (p < 0.05) and the presence of tumour cells in bone marrow (p < 0.05). Tumours expressing high levels of VEGF-D showed significantly advanced stages of tumour infiltration (p < 0.05) and lymph node metastasis (p < 0.01).

Conclusions

VEGF-A is a significant marker for the presence of tumour cells in the bone marrow of gastric cancer patients. Our results confirm VEGF-D as a predictor for the lymphatic spread of tumour cells. Therefore, the route of metastatic spread of gastric cancer could be determined, at least in part, by the profile of VEGF family members expressed in the primary tumour of gastric cancer patients.     

Prognostic impact of nodal micrometastasis in early esophageal cancer

Introduction

Nodal micrometastasis is a negative prognosticator for esophageal cancer. There is a trend toward endoscopic resection for early cancer of the esophagus without lymphadenectomy. Frequency and prognostic impact of nodal micrometastasis in early cancer of the esophagus have not been investigated so far.

Patients and methods

This study includes 69 patients with a pT1-stage cancer of the esophagus (SCC: n = 26, AC: n = 43), who underwent transthoracic en-bloc esophagectomy with D2-lympadenectomy between 1996 and 2004. On routine histopathological analysis 48 patients were diagnosed as pN0. Lymph nodes (n = 1344) of these patients were further examined for the presence of isolated tumor cells with the monoclonal anti-epithelial antibody AE1/AE3.

Results

In lymph nodes of 7 (14.6%) out of 48 pN0-patients a positive staining for AE1/AE3 as a sign for nodal micrometastasis was found. In these patients the tumor has infiltrated the submucosal layer. In patients with tumors restricted to mucosal layer (n = 20) no nodal micrometastasis was present. 5-year survival of pN0-patients with nodal micrometastasis was inferior compared to pN0-patients (57% vs. 82%; p = 0.002).

Conclusion

Almost 15% of patients with pT1 N0 M0 carcinoma of the esophagus and only those with submucosal infiltration show nodal micrometastasis. It has a significant negative impact on survival already in early esophageal cancer.     

“Axillary recurrences after sentinel lymph node biopsy: A multicentre analysis and follow-up of sentinel lymph node negative breast cancer patients”

Introduction

The objective of this study was to conduct a multicentre data analysis to identify prognostic factors for developing an axillary recurrence (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast cancer patients with long follow-up.

Patients and methods

The prospective databases from different hospitals of clinically node negative breast cancer patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and pathological analysis done by local pathologists according to national guidelines. Adjuvant treatment was given according to contemporary guidelines. Multivariate analysis was performed using all available variables, a p-value of <0,05 was considered to be significant.

Results

A total of 929 patients who did not undergo axillary lymph node dissection were identified. After a median follow up of 77 (range 1–106) months, fifteen patients developed an isolated AR (AR rate 1,6%). Multivariate analysis showed that young age (p = 0.007) and the absence of radiotherapy (p = 0.010) significantly increased the risk of developing an AR. Distant metastasis free survival (DMFS) was significantly worse for patients with an AR compared to all other breast cancer patients (p < 0,0001).

Conclusion

Even after long-term follow up, the risk of developing an AR after a negative SLN in breast cancer is low. Young age and absence of radiation therapy are highly significant factors for developing an axillary recurrence. DMFS is worse for AR patients compared to patients initially diagnosed with N0 or N1 disease.